The goal of this Research Career Award is to investigate the possible genetic link between executive cognitive function (ECF) and clinical antecedents of substance use disorders, namely conduct disorder (CD) and attention deficit hyperactivity disorder (ADHD); psychiatric syndromes which show high comorbidity. Although the association between ECF deficits and these developmental disorders has been demonstrated in previous work, little research has been done to uncover the source of this association. Understanding the etiology of these frequently comorbid syndromes may begin to bridge an important neurobiological gap between genetic and environment risk/protective factors and clinical outcomes. The training application includes: 1) direct instruction and supervision by experts in neuropsychology, developmental psychopathology, and methodology; 2) completion of several courses and seminars aimed at gaining a foundation in neuroscience and neuropsychology; 3) participation in workshops offering training in twin research methodology as well as genetic association and linkage analysis; and 4) participation in professional conferences. The research application aims to study 600 male and female adolescent twins (300 pairs), selected for indicators of risk for the development of these disorders. These twins will be a subsample of twins participating in an ongoing study of heritable early indicators of risk for drug dependence (DA-11015), who have been assessed for a wide-range of child psychopathology and substance use patterns, as well as measures of personality and behavioral development. The proposed research will supplement these previously collected assessments with a battery of standardized measures of ECF in order to examine the role of ECF in the development of CD, ADHD and substance use (SU). The study design employs a multi-stage analysis. First, we will test phenotypic models to identify which characteristics of ECF best predict severity of clinical outcome. We hypothesize that deficits in the ability to inhibit inappropriate responding (e.g., impulse control) will strongly predict symptom severity of CD, ADHD and SU, and will be significant markers of comorbidity among the disorders. The second aim is to use multivariate behavior genetic analyses to examine the extent to which variation in ECF is mediated by genetic and/or environmental factors. Our final aim is to determine the extent to which the covariation between ECF deficits and comorbid psychopathology is due to genetic and/or environmental factors.